African tick bite fever (ATBF) is a bacterial infection spread by the bite of a tick.[1] Symptoms may include fever, headache, muscles pains, and a rash,[1] at the site of the bite there is typically a red skin sore with a dark center.[1] Onset usually occur 4–10 days after the bite.[4] Complications are rare, however may include joint inflammation,[2][3] some people do not develop symptoms.[4]

African tick bite fever is often asymptomatic or mild in clinical presentation and complications are rare,[6] the onset of illness is typically 5–7 days after the tick bite, although in some cases it may take up to 10 days for symptoms to occur.[7] Symptoms can persist for several days to up to three weeks.[6] Common presenting symptoms include:

Inoculation eschar, which is dead, often black, tissue around a bite site[7] (see photo above)

Eschars may or may not be present. Amblyomma ticks actively attack cattle or humans and can bite more than once.[4] In African tick bite fever, unlike what is typically seen with other Rickettsial spotted fevers when only one eschar is identified, multiple eschars may be seen and are considered pathognomonic.[7]

Two species of hard ticks, Amblyoma variegatum and Amblyomma hebraeum are the most common vectors of R. africae.[10] Typically, Amblyoma variegatum transmits the bacteria in South Africa while Amblyomma hebraeum carries R. africae throughout West, Central and East Africa and through the French West Indies.[10] Other species of Amblyomma in sub-Saharan Africa can also transmit R. africae and it may be that up to 100% of Amblyomma ticks in sub-Saharan Africa carry R. africae.[8]Amblyomma ticks are most active from November to April.[1] These tick species frequently feed on cattle and other livestock, but can also be found feeding on wild animals in areas where farm animals are not found.[7] Unlike other hard tick species, which passively seek hosts by clinging to plants and waiting for a potential host to brush by in passing, the Amblyomma hard ticks actively seek out hosts.

Groups of tourists visiting Africa have returned to their own countries and were diagnosed there as having been infected.[11][12]

Up until 1998, it was thought that only ticks in sub-Saharan Africa carried R. africae. However, a case of locally transmitted African tick bite fever in the French West Indies led to the discovery of R. africae carried by Amblyomma varigatum ticks introduced through cattle shipped from Senegal to Gaudeluope more than a century ago.[10]R. africae has been isolated from ticks on several Caribbean islands, though the only cases in humans in the Caribbean have occurred in the French West Indies.[8]R. africae has also been found in Amblyomma loculosum ticks in Oceania.[4]

After the rickettsia bacteria infects humans through a tick bite, it invades endothelial cells in the circulatory system (veins, arteries, capillaries),[13] the body then releases chemicals that cause inflammation, resulting in the characteristic symptoms like headache and fever. The hallmark of all rickettsial diseases is a histology (cellular) finding called lymphohistiocytic vasculitis[14] that involves immune cell deposition into the endothelial cells that make up vessels.[7] This occurs secondary to the chemicals mentioned above, as well as damage from the infection, and involves signals to immune cells (T cells and macrophages) to come to the site of the infection.[15]

Rickettsia bacteria species like R. africae replicate around the area of the initial tick bite, causing necrosis (cell death) and lymph node inflammation.[13] This is the cause of the characteristic eschar.[13]

Many patients with ATBF who live in areas with a high number of infections (Africa and the West Indies) do not visit a doctor, as most patients only have mild symptoms,[6] this disease can, however, cause more serious symptoms in travelers who have never been exposed to the Rickettsia africae bacterium before and are not immune.[16] Travelers who present to a doctor after a trip to affected areas can be hard to diagnose, as many tropical diseases cause a fever similar to that of ATBF.[17] Other diseases that may look similar are malaria, dengue fever, tuberculosis, acute HIV and respiratory infections;[17] in addition to questions about symptoms, doctors will ask patients for an accurate travel history and whether he/she was near animals or ticks.[17] Microbiological tests are available for doctors, but are expensive and often must be done by special laboratories.[18]

The antibiotic treatment available for rickettsiae infections has very few side effects, so if a doctor has a high suspicion of the disease, he or she may simply treat without doing more laboratory tests.[3]

Diagnosis of ATBF is mostly based on symptoms, as many laboratory tests are not specific for ATBF. Common laboratory test signs of ATBF are a low white blood cell count (lymphopenia) and low platelet count (thrombocytopenia), a high C-reactive protein, and mildly high liver function tests.[18]

Biopsies or cultures of a person's tick wound (eschar) are used to diagnose ATBF. However, this requires special culture media and can only be done by a laboratory with biohazard protection.[18] There are more specialized laboratory tests available that use quantitative polymerase chain reactions (qPCR), but can only be done by laboratories with special equipment.[18]Immunofluorescence assays can also be used, but are hard to interpret because of cross-reactions with other rickettsiae bacteria.[8]

Prevention of ATBF centers around protecting oneself from tick bites by wearing long pants and shirt, and using insecticides like DEET on the skin.[7] Travelers to rural areas in Africa and the West Indies should be aware that they may come in contact with ATBF tick vectors.[7] Infection is more likely to occur in people who are traveling to rural areas or plan to spend time participating in outdoor activities. Extra caution should be taken in November - April, when Amblyomma ticks are more active.[1] Inspection of the body, clothing, gear, and any pets after time outdoors can help to identify and remove ticks early.[1]

African tick bite fever is usually mild, and most patients do not need more than at-home treatment with antibiotics for their illness.[6] However, because so few patients with this infection visit a doctor, the best antibiotic choice, dose and length of treatment are not well known.[8] Typically doctors treat this disease with antibiotics that have been used effectively for the treatment of other diseases caused by bacteria of similar species, such as Rocky Mountain Spotted Fever,[8] for mild cases, people are usually treated with one of the following:

If a person has more severe symptoms, like a high fever or serious headache, the infection can be treated with doxycycline for a longer amount of time.[7] Pregnant women should not use doxycycline or ciprofloxacin as both antibiotics can cause problems in fetuses.[19]Josamycin has been used effectively for treatment of pregnant women with other rickettsial diseases, but it is unclear if it has a role in the treatment of ATBF.[7]

Cases of African tick bite fever have been more frequently reported in the literature among international travelers.[7] Data examining rates in local populations are limited,[7] among locals who live in endemic areas, exposure at a young age and mild symptoms or lack of symptoms, as well as decreased access to diagnostic tools, may lead to decreased diagnosis.[20] In Zimbabwe, where R. africae is endemic, one study reported an estimated yearly incidence of 60-80 cases per 10,000 patients.[7][20]

Looking at published data over the past 35 years, close to 200 confirmed cases of African tick bite fever in international travelers have been reported, the majority (~80%) of these cases occurred in travelers returning from South Africa.[7]

1.
Medical diagnosis
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Medical diagnosis is the process of determining which disease or condition explains a persons symptoms and signs. It is most often referred to as diagnosis with the context being implicit. The information required for diagnosis is typically collected from a history, often, one or more diagnostic procedures, such as diagnostic tests, are also done during the process. Sometimes Posthumous diagnosis is considered a kind of medical diagnosis, Diagnosis is often challenging, because many signs and symptoms are nonspecific. For example, redness of the skin, by itself, is a sign of many disorders, thus differential diagnosis, in which several possible explanations are compared and contrasted, must be performed. This involves the correlation of various pieces of information followed by the recognition and differentiation of patterns, occasionally the process is made easy by a sign or symptom that is pathognomonic. Diagnosis is a component of the procedure of a doctors visit. From the point of view of statistics, the procedure involves classification tests. The first recorded examples of medical diagnosis are found in the writings of Imhotep in ancient Egypt, a Babylonian medical textbook, the Diagnostic Handbook written by Esagil-kin-apli, introduced the use of empiricism, logic and rationality in the diagnosis of an illness or disease. Traditional Chinese Medicine, as described in the Yellow Emperors Inner Canon or Huangdi Neijing, specified four diagnostic methods, inspection, auscultation-olfaction, interrogation, hippocrates was known to make diagnoses by tasting his patients urine and smelling their sweat. This article uses diagnostician as any of these person categories, a diagnostic procedure does not necessarily involve elucidation of the etiology of the diseases or conditions of interest, that is, what caused the disease or condition. Such elucidation can be useful to optimize treatment, further specify the prognosis or prevent recurrence of the disease or condition in the future, the initial task is to detect a medical indication to perform a diagnostic procedure. Indications include, Detection of any deviation from what is known to be normal, such as can be described in terms of, for example, anatomy, physiology, pathology, psychology, a complaint expressed by a patient. The fact that a patient has sought a diagnostician can itself be an indication to perform a diagnostic procedure, even during an already ongoing diagnostic procedure, there can be an indication to perform another, separate, diagnostic procedure for another, potentially concomitant, disease or condition. A diagnostic test is any kind of medical test performed to aid in the diagnosis or detection of disease, Diagnostic tests can also be used to provide prognostic information on people with established disease. Processing of the answers, findings or other results, consultations with other providers and specialists in the field may be sought. There are a number of methods or techniques that can be used in a diagnostic procedure, in reality, a diagnostic procedure may involve components of multiple methods. The final result may also remain a list of possible conditions, the resultant diagnostic opinion by this method can be regarded more or less as a diagnosis of exclusion

2.
Microbiological culture
–
A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested and it is one of the primary diagnostic methods of microbiology and used as a tool to determine the cause of infectious disease by letting the agent multiply in a predetermined medium. Furthermore, the culture is more generally used informally to refer to selectively growing a specific kind of microorganism in the lab. Microbial cultures are foundational and basic methods used extensively as a research tool in molecular biology. It is often essential to isolate a pure culture of microorganisms, a pure culture is a population of cells or multicellular organisms growing in the absence of other species or types. A pure culture may originate from a cell or single organism. For the purpose of gelling the microbial culture, the medium of agarose gel is used, agar is a gelatinous substance derived from seaweed. A cheap substitute for agar is guar gum, which can be used for the isolation, there are several types of bacterial culture methods that are selected based on the agent being cultured and the downstream use. One method of culture is liquid culture, in which the desired bacteria are suspended in a liquid nutrient medium, such as Luria Broth. This allows a scientist to grow up large amounts of bacteria for a variety of downstream applications, liquid cultures are ideal for preparation of an antimicrobial assay in which the experimenter inoculates liquid broth with bacteria and lets it grow overnight. Then they would take aliquots of the sample to test for the activity of a specific drug or protein. As an alternative, the microbiologist may decide to use static liquid cultures and these cultures are not shaken and they provide the microbes with an oxygen gradient. Microbiological cultures can be grown in petri dishes of differing sizes that have a layer of agar-based growth medium. Once the growth medium in the dish is inoculated with the desired bacteria. After the desired level of growth is achieved, agar plates can be stored upside down in a refrigerator for a period of time to keep bacteria for future experiments. There are a variety of additives that can be added to agar before it is poured into a plate, some types of bacteria can only grow in the presence of certain additives. This can also be used when creating engineered strains of a bacteria that contain an antibiotic-resistance gene, when the selected antibiotic is added to the agar, only bacterial cells containing the gene insert conferring resistance will be able to grow. This allows the researcher to select only the colonies that were successfully transformed, stab cultures are similar to agar plates, but are formed by solid agar in a test tube

3.
Polymerase chain reaction
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It is an easy, cheap, and reliable way to repeatedly replicate a focused segment of DNA, a concept which is applicable to numerous fields in modern biology and related sciences. Developed in 1983 by Kary Mullis, PCR is now a common and often indispensable technique used in clinical, in 1993, Mullis was awarded the Nobel Prize in Chemistry along with Michael Smith for his work on PCR. Primers containing sequences complementary to the region, along with a DNA polymerase, after which the method is named, enable selective. As PCR progresses, the DNA generated is used as a template for replication. The simplicity of the principle underlying PCR means it can be extensively modified to perform a wide array of genetic manipulations. PCR is not generally considered to be a recombinant DNA method, as it does not involve cutting and pasting DNA, almost all PCR applications employ a heat-stable DNA polymerase, such as Taq polymerase, an enzyme originally isolated from the thermophilic bacterium Thermus aquaticus. In the first step, the two strands of the DNA double helix are physically separated at a temperature in a process called DNA melting. In the second step, the temperature is lowered and the two DNA strands become templates for DNA polymerase to amplify the target DNA. The selectivity of PCR results from the use of primers that are complementary to the DNA region targeted for amplification under specific thermal cycling conditions, PCR amplifies a specific region of a DNA strand. Most PCR methods amplify DNA fragments of between 0.1 and 10 kilo base pairs, although some techniques allow for amplification of fragments up to 40 kbp in size. The amount of amplified product is determined by the available substrates in the reaction, the thermal cycler heats and cools the reaction tubes to achieve the temperatures required at each step of the reaction. Many modern thermal cyclers make use of the Peltier effect, which permits both heating and cooling of the holding the PCR tubes simply by reversing the electric current. Thin-walled reaction tubes permit favorable thermal conductivity to allow for rapid thermal equilibration, most thermal cyclers have heated lids to prevent condensation at the top of the reaction tube. Older thermal cyclers lacking a heated lid require a layer of oil on top of the mixture or a ball of wax inside the tube. Typically, PCR consists of a series of 20–40 repeated temperature changes, called cycles, the cycling is often preceded by a single temperature step at a very high temperature, and followed by one hold at the end for final product extension or brief storage. The individual steps common to most PCR methods are as follows, Initialization and it consists of heating the reaction chamber to a temperature of 94–96 °C, or 98 °C if extremely thermostable polymerases are used, which is then held for 1–10 minutes. Denaturation, This step is the first regular cycling event and consists of heating the reaction chamber to 94–98 °C for 20–30 seconds and this causes DNA melting, or denaturation, of the double-stranded DNA template by breaking the hydrogen bonds between complementary bases, yielding two single-stranded DNA molecules. Annealing, In the next step, the temperature is lowered to 50–65 °C for 20–40 seconds

4.
Immunofluorescence
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Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. The specific region an antibody recognizes on an antigen is called an epitope, there have been efforts in epitope mapping since many antibodies can bind the same epitope and levels of binding between antibodies that recognize the same epitope can vary. Additionally, the binding of the fluorophore to the antibody itself cannot interfere with the specificity of the antibody or the binding capacity of its antigen. Immunofluorescence is a used example of immunostaining and is a specific example of immunohistochemistry. This technique primarily makes use of fluorophores to visualise the location of the antibodies and this technique can even be used to visualize structures such as intermediate-sized filaments. If the topology of a membrane has yet to be determined. Immunofluorescence can be used in combination with other, non-antibody methods of fluorescent staining, for example, several microscope designs can be used for analysis of immunofluorescence samples, the simplest is the epifluorescence microscope, and the confocal microscope is also widely used. Various super-resolution microscope designs that are capable of higher resolution can also be used. To make fluorochrome-labeled antibodies, a fluorochrome must be conjugated to the antibody, likewise, an antigen can also be conjugated to the antibody with a fluorescent probe in a technique called fluorescent antigen technique. Staining procedures can apply to both fixed antigen in the cytoplasm or to surface antigens on live cells, called membrane immunofluorescence. It is also possible to label the complement of the complex with a fluorescent probe. In addition to the element to which fluorescence probes are attached, the following descriptions will focus primarily on these classes in terms of conjugated antibodies. There are two classes of immunofluorescence techniques, primary and secondary, primary immunofluorescence uses a single, primary antibody, chemically linked to a fluorophore. The primary antibody recognizes the molecule and binds to a specific region called the epitope. The attached fluorophore can be detected via fluorescent microscopy, which, depending on the messenger used, direct immunofluorescence, although somewhat less common, has notable advantages over the secondary procedure. The direct attachment of the messenger to the antibody reduces the number of steps in the procedure, saving time and this also limits the possibility of antibody cross-reactivity and possible mistakes throughout the process. However, some disadvantages do exist in this method, direct immunofluorescence also requires the use of much more primary antibody, which is extremely expensive, sometimes running up to $400. 00/mL. Multiple secondary antibodies can bind a single primary antibody and this provides signal amplification by increasing the number of fluorophore molecules per antigen

5.
Sub-Saharan Africa
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Sub-Saharan Africa is, geographically, the area of the continent of Africa that lies south of the Sahara. According to the UN, it consists of all African countries that are fully or partially located south of the Sahara and it contrasts with North Africa, whose territories are part of the League of Arab states within the Arab world. Somalia, Djibouti, Comoros and Mauritania are geographically in Sub-Saharan Africa, the Sahel is the transitional zone between the Sahara and the tropical savanna and forest-savanna mosaic to the south. The Sahara pump theory explains how flora and fauna left Africa to penetrate the Middle East, African pluvial periods are associated with a wet Sahara phase during which larger lakes and more rivers existed. Geographers historically divided the region into several distinct ethnographic sections based on each areas respective inhabitants, commentators in Arabic in the medieval period used the general term bilâd as-sûdân for the vast Sudan region, or sometimes extending from the coast of West Africa to Western Sudan. Its equivalent in Southeast Africa was Zanj, which was situated in the vicinity of the Great Lakes region. The geographers drew an explicit distinction between the Sudan region and its analogue Zanj, from the area to their extreme east on the Red Sea coast in the Horn of Africa. In modern-day Ethiopia and Eritrea was Al-Habash or Abyssinia, which was inhabited by the Habash or Abyssinians, Sub-Saharan Africa has a wide variety of climate zones or biomes. South Africa and the Democratic Republic of the Congo in particular are considered Megadiverse countries, the Sahel shoots across all of Africa at a latitude of about 10° to 15° N. Countries that include parts of the Sahara Desert proper in their territories and parts of the Sahel in their southern region include Mauritania, Mali, Niger, Chad. The Sahel has a hot semi-arid climate, South of the Sahel, there is a belt of savanna, widening to include most of South Sudan and Ethiopia in the east. The Serengeti ecosystem is located in northwestern Tanzania and extends to southwestern Kenya, the Kalahari Basin includes the Kalahari Desert surrounded by a belt of semi-desert. The Bushveld is a tropical ecoregion of Southern Africa. The Karoo is a semi-desert in western South Africa and this occurred 10 million to 5 million years ago. By 3 million years ago several australopithecine hominid species had developed throughout southern, eastern and they were tool users rather than tool manufacturers. The tools were classed as Oldowan, roughly 1.8 million years ago, Homo ergaster first appeared in the fossil record in Africa. From Homo ergaster, Homo erectus evolved 1.5 million years ago, some of the earlier representatives of this species were small-brained and used primitive stone tools, much like H. habilis. The brain later grew in size, and H. erectus eventually developed a complex stone tool technology called the Acheulean

6.
Tick
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Ticks are small arachnids, part of the order Parasitiformes. Along with mites, they constitute the subclass Acari, Ticks are ectoparasites, living by feeding on the blood of mammals, birds, and sometimes reptiles and amphibians. Ticks had evolved by the Cretaceous period, the most common form of fossilisation being immersed in amber, Ticks are widely distributed around the world, especially in warm, humid climates. Almost all ticks belong to one of two families, the Ixodidae or hard ticks, which are difficult to crush. Adults have ovoid or pear-shaped bodies which become engorged with blood when they feed, both families locate a potential host by odour or from changes in the environment. Ticks have four stages to their lifecycle, namely egg, larva, nymph, ixodid ticks have three hosts, taking at least a year to complete their lifecycle. Argasid ticks have up to seven stages, each one requiring a blood meal. Because of their habit of ingesting blood, ticks are vectors of at least twelve diseases that affect humans, fossilized ticks are known from the Cretaceous onwards, most commonly in amber. They most likely originated in the Cretaceous, with most of the evolution, the oldest example is an argasid bird tick from Cretaceous New Jersey amber. The younger Baltic and Dominican ambers have also yielded examples which can be placed in living genera, there are three families of ticks. The two large ones are the families of Ixodidae and Argasidae. The third is Nuttalliellidae, named for the bacteriologist George Nuttall and it comprises a single species, Nuttalliella namaqua, and is the most basal lineage. Ticks are closely related to the mites, within the subclass Acarina, RDNA analysis suggests that the Ixodidae are a clade, but that the Argasidae may be paraphyletic. The Ixodidae contains over 700 species of ticks with a scutum or hard shield. The Argasidae contains about 200 species, the genera accepted as of 2010 are Antricola, Argas, Nothoaspis, Ornithodoros and they have no scutum, and the capitulum is concealed beneath the body. The family Nuttalliellidae contains only a species, Nuttalliella namaqua. The phylogeny of the Ixodida within the Acari is shown in the cladogram, the Argasidae appear monophyletic in this study. Ticks are also distributed among host taxa, which include marsupial and placental mammals, birds, reptiles such as snakes, iguanas and lizards

7.
Vaccine
–
A vaccine is a biological preparation that provides active acquired immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is made from weakened or killed forms of the microbe. Vaccines can be prophylactic, or therapeutic, the administration of vaccines is called vaccination. The effectiveness of vaccination has been studied and verified, for example, the influenza vaccine, the HPV vaccine. The World Health Organization reports that licensed vaccines are available to prevent or contribute to the prevention. The terms vaccine and vaccination are derived from Variolae vaccinae, the term devised by Edward Jenner to denote cowpox. He used it in 1798 in the title of his Inquiry into the. Variolae vaccinae. known. the Cow Pox. In 1881, to honor Jenner, Louis Pasteur proposed that the terms should be extended to cover the new protective inoculations then being developed, vaccines have historically been the most effective means to fight and eradicate infectious diseases. Limitations to their effectiveness, nevertheless, exist, sometimes, protection fails because the hosts immune system simply does not respond adequately or at all. Lack of response commonly results from factors such as diabetes, steroid use. Adjuvants commonly are used to boost immune response, particularly for older people, the efficacy or performance of the vaccine is dependent on a number of factors, the disease itself the strain of vaccine whether the vaccination schedule has been properly observed. Idiosyncratic response to vaccination, some individuals are non-responders to certain vaccines, assorted factors such as ethnicity, age, or genetic predisposition. If a vaccinated individual does develop the disease vaccinated against, the disease is likely to be less virulent than in unvaccinated victims, in 1958, there were 763,094 cases of measles in the United States,552 deaths resulted. After the introduction of new vaccines, the number of cases dropped to fewer than 150 per year, in early 2008, there were 64 suspected cases of measles. Vaccines have contributed to the eradication of smallpox, one of the most contagious, other diseases such as rubella, polio, measles, mumps, chickenpox, and typhoid are nowhere near as common as they were a hundred years ago. As long as the vast majority of people are vaccinated, it is more difficult for an outbreak of disease to occur. This effect is called herd immunity, polio, which is transmitted only between humans, is targeted by an extensive eradication campaign that has seen endemic polio restricted to only parts of three countries. However, the difficulty of reaching all children as well as cultural misunderstandings have caused the anticipated eradication date to be missed several times, vaccination given during childhood is generally safe

8.
DEET
–
N, N-Diethyl-meta-toluamide, also called DEET or diethyltoluamide, is the most common active ingredient in insect repellents. It is a yellow oil intended to be applied to the skin or to clothing, and provides protection against mosquitoes, ticks, fleas, chiggers, leeches. DEET was developed in 1944 by Samuel Gertler of the United States Department of Agriculture for use by the United States Army and it was originally tested as a pesticide on farm fields, and entered military use in 1946 and civilian use in 1957. It was used in Vietnam and Southeast Asia, in its original form known as bug juice, the application solution for DEET was composed of 75% DEET and ethanol. Later, a new application of the repellant was developed by U. S. Army and this extended release application was registered by the EPA in 1991. The prevailing theory was that DEET effectively blinds the insects senses so that the instinct is not triggered by humans or other animals which produce these chemicals. DEET does not appear to affect the ability to smell carbon dioxide. However, more recent evidence shows that DEET serves as a true repellent in that mosquitoes intensely dislike the smell of the chemical. Moreover, in a behavioral test, DEET had a strong repellent activity in the absence of body odor attractants such as 1-octen-3-ol, lactic acid, both female and male mosquitoes showed the same response. A2013 study suggests that mosquitoes can at least temporarily overcome or adapt to the repellent effect of DEET after an initial exposure and this observation, if verified, has significant implications for how repellent effectiveness should be assessed. A highly conserved protein member of the ionotropic receptor family, IR40a, has recently identified as a putative DEET receptor in the fly antenna. The neurons expressing IR40a respond to DEET in an IR40a dependent manner, avoidance to DEET vapors is lost in flies that lack IR40a. Other repellent chemicals that are related to DEET also activate the same receptor and repel mosquitoes and flies. The hypothesis that IR40a is involved in DEET reception in mosquitoes has been tested in the southern house mosquito, reducing CquiIR40a transcript levels did not affect DEET-elicited behavior or electroantennographic responses thus suggesting that IR40a is not involved in DEET reception in Culex mosquitoes. An antennae-specific odorant receptor, CquiOR136, was demonstrated to respond to DEET, similar knockout experiments showed that EAG responses to DEET recorded from mosquitoes with reduced CquiOR136 transcript levels were dramatically lower. Additionally, behavioral tests showed that this phenotype was not repelled by DEET, in conclusion, these results suggest that CquiOR136, not CquiIR40a, is involved in DEET reception in the southern house mosquito. DEET is often sold and used in spray or lotion in concentrations up to 100%, consumer Reports found a direct correlation between DEET concentration and hours of protection against insect bites. 100% DEET was found to offer up to 12 hours of protection while several lower concentration DEET formulations offered 3–6 hours of protection, other research has corroborated the effectiveness of DEET

9.
Permethrin
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Permethrin, sold under the brand name Nix among others, is a medication and insecticide. As a medication it is used to treat scabies and lice and it is applied to the skin as a cream or lotion. As an insecticide it can be sprayed on clothing or mosquito nets such that the insects that touch them die, side effects include rash and irritation at the area of use. Use during pregnancy appears to be safe and it is approved for use in people over the age of two months. Permethrin is in family of medications. It works by disrupting the function of the neurons of lice and it is on the World Health Organizations List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the world is about 0.02 to 0.06 USD per gram. In the United States a course of treatment costs 25 to 50 USD, permethrin is available for topical use as a cream or lotion. It is indicated for the treatment and prevention in exposed individuals of head lice, for treatment of scabies, Adults and children older than 2 months are instructed to apply the cream to the entire body from head to the soles of the feet. Wash off the cream after 8–14 hours, in general, one treatment is curative. For treatment of lice, Apply to hair, scalp. Leave in for 10 minutes and rinse, in agriculture, permethrin is mainly used on cotton, wheat, maize, and alfalfa crops. Its use is controversial because, as a chemical, it kills indiscriminately, as well as the intended pests, it can harm beneficial insects including honey bees. Permethrin kills ticks on contact with treated clothing, a method of reducing deer tick populations by treating rodent vectors involves stuffing biodegradable cardboard tubes with permethrin-treated cotton. Mice collect the cotton for lining their nests, permethrin on the cotton instantly kills any immature ticks feeding on the mice. Permethrin is used in areas to prevent mosquito-borne disease such as dengue fever. Mosquito nets used to cover beds may be treated with a solution of permethrin and this increases the effectiveness of the bed net by killing parasitic insects before they are able to find gaps or holes in the net. Military personnel training in malaria-endemic areas may be instructed to treat their uniforms with permethrin, permethrin is the most commonly used insecticide worldwide for the protection of wool from keratinophagous insects such as Tineola bisselliella

10.
Antibiotic
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Antibiotics, also called antibacterials, are a type of antimicrobial drug used in the treatment and prevention of bacterial infections. They may either kill or inhibit the growth of bacteria, a limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the cold or influenza. Drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics, sometimes the term antibiotic is used to refer to any substance used against microbes, synonymous with antimicrobial. Some sources distinguish between antibacterial and antibiotic, antibacterials are used in soaps and disinfectants, while antibiotics are used as medicine, Antibiotics revolutionized medicine in the 20th century, and have together with vaccination led to the near eradication of diseases such as tuberculosis in the developed world. However, their effectiveness and easy access led to overuse, especially in raising, prompting bacteria to develop resistance. All classes of antibiotics in use today were first discovered prior to the mid 1980s, substances with antibiotic properties had been used for various purposes since ancient times. Before the early 20th century, treatments for infections were based primarily on medicinal folklore, mixtures with antimicrobial properties that were used in treatments of infections were described over 2000 years ago. Many ancient cultures, including the ancient Egyptians and ancient Greeks, used specially selected mold and plant materials, more recent observations made in the laboratory of antibiosis between microorganisms led to the discovery of natural antibacterials produced by microorganisms. Louis Pasteur observed, if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics. In 1874, physician Sir William Roberts noted that cultures of the mold Penicillium glaucum that is used in the making of types of blue cheese did not display bacterial contamination. In 1876, physicist John Tyndall also contributed to this field, Louis Pasteur conducted research showing that Bacillus anthracis would not grow in the presence of the related mold Penicillium notatum. In his thesis, Duchesne proposed that bacteria and molds engage in a battle for survival. Duchesne observed that E. coli was eliminated by the fungus Penicillium glaucum when they were grown in the same culture. He also observed that when he inoculated animals with lethal doses of typhoid bacilli together with Penicillium glaucum. Unfortunately Duchesnes army service after getting his degree prevented him from doing any further research, Duchesne died of tuberculosis, a disease now treated by antibiotics. In 1928, Sir Alexander Fleming identified penicillin, a molecule produced by molds that kills or stops the growth of certain kinds of bacteria. Fleming was working on a culture of disease-causing bacteria when he noticed the spores of a mold, Penicillium chrysogenum

11.
West Indies
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Indigenous peoples were the first inhabitants of the West Indies. In 1492, Christopher Columbus became the first European to arrive at the islands, after the first of the voyages of Christopher Columbus to the Americas, Europeans began to use the term West Indies to distinguish the region from the East Indies of South Asia and Southeast Asia. In the late century, French, English and Dutch merchants and privateers began their operations in the Caribbean Sea, attacking Spanish and Portuguese shipping. These African slaves wrought a demographic revolution, replacing or joining with either the indigenous Caribs or the European settlers who were there as indentured servants. The Dutch, allied with the Caribs of the Orinoco would eventually carry the struggles deep into South America, first along the Orinoco and these interconnected commercial and diplomatic relations made up the Western Caribbean Zone which was in place in the early eighteenth century. In 1916, Denmark sold the Danish West Indies to the United States for US$25 million in gold, the Danish West Indies became an insular area of the US, called the United States Virgin Islands. Between 1958 and 1962, the United Kingdom re-organised all their West Indies island territories into the West Indies Federation and they hoped that the Federation would coalesce into a single, independent nation. West Indian is the term used by the U. S. government to refer to people of the West Indies. Tulane University professor Rosanne Adderly says he phrase West Indies distinguished the territories encountered by Columbus, … The term West Indies was eventually used by all European nations to describe their own acquired territories in the Americas. Despite the collapse of the Federation … the West Indies continues to field a joint cricket team for international competition, the West Indies cricket team includes participants from Guyana, which is geographically located in South America. More than Slaves and Sugar, Recent Historiography of the Trans-imperial Caribbean, a Concise History of the Caribbean. Martin, Tony, Caribbean History, From Pre-colonial Origins to the Present

12.
Oceania
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Oceania, also known as Oceanica, is a region centred on the islands of the tropical Pacific Ocean. The term is used more specifically to denote a continent comprising Australia. The term was coined as Océanie circa 1812 by geographer Conrad Malte-Brun, the word Océanie is a French word derived from the Latin word oceanus, and this from the Greek word ὠκεανός, ocean. Natives and inhabitants of this region are called Oceanians or Oceanicans, as an ecozone, Oceania includes all of Micronesia, Fiji, and all of Polynesia except New Zealand. New Zealand, along with New Guinea and nearby islands, part of the Philippine islands, Australia, the Solomon Islands, Vanuatu, in geopolitical terms, however, New Zealand, the Solomon Islands, Vanuatu and New Caledonia are almost always considered part of Oceania. Australia and Papua New Guinea are usually considered part of Oceania along with the Maluku Islands, puncak Jaya in Papua is often considered the highest peak in Oceania. Oceania was originally conceived as the lands of the Pacific Ocean and it comprised four regions, Polynesia, Micronesia, Malaysia, and Melanesia. The area extends to Sumatra in the west, the Bonin Islands in the northwest, the Hawaiian Islands in the northeast, Rapa Nui and Sala y Gómez Island in the east, and Macquarie Island in the south. Not included are the Pacific islands of Taiwan, the Ryukyu Islands and the Japanese archipelago, all on the margins of Asia, and the Aleutian Islands of North America. The islands at the extremes of Oceania are Bonin, a politically integral part of Japan, Hawaii, a state of the United States. There is also a geographic definition that excludes land on the Sunda Plate. Biogeographically, Oceania is used as a synonym for either the Australasian ecozone or the Pacific ecozone, Oceania is one of eight terrestrial ecozones, which constitute the major ecological regions of the planet. The Oceania ecozone includes all of Micronesia, Fiji, and all of Polynesia except New Zealand, New Zealand, New Guinea, Melanesia apart from Fiji, and Australia constitute the separate Australasian ecozone. The Malay Archipelago is part of the Indomalaya ecozone, related to these concepts are Near Oceania, that part of western Island Melanesia which has been inhabited for tens of millennia, and Remote Oceania which is more recently settled. The term is used to denote a continent comprising Australia. New Zealand forms the corner of the Polynesian Triangle. Its indigenous Māori constitute one of the cultures of Polynesia. It is also, however, considered part of Australasia, the history of Oceania in the medieval period was synonymous with the history of the indigenous peoples of Australasia, Micronesia, Melanesia, Polynesia

13.
Eschar
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The term eschar is not interchangeable with scab. An eschar contains necrotic tissue, whereas a scab is composed of dried blood, black eschars are most commonly attributed to anthrax, which may be contracted through herd animal exposure, but can also be obtained from Pasteurella multocida exposure in cats and rabbits. A newly identified human rickettsial infection, R. parkeri rickettsiosis, Eschar is sometimes called a black wound because the wound is covered with thick, dry, black necrotic tissue. Eschar may be allowed to slough off naturally, or it may require surgical removal to prevent infection, if eschar is on a limb, it is important to assess peripheral pulses of the affected limb to make sure blood and lymphatic circulation is not compromised. If circulation is compromised, an escharotomy, or surgical incision through the eschar, an escharotic is a substance that causes tissue to die and slough off. Examples include acids, alkalis, carbon dioxide, metallic salts and sanguinarine, consequently, escharotic salves are very strictly regulated in most western countries and while some prescription medicines are available with this effect, unauthorized sales are illegal. Some prosecutions have been pursued over unlicensed sales of products such as Cansema. Wound healing Medical Separation of the Eschar

14.
Rickettsia
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Rickettsia is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that can be present as cocci, rods, or thread-like. The term rickettsia, named after Howard Taylor Ricketts, is used interchangeably for any member of the Rickettsiales. Being obligate intracellular parasites, the Rickettsia survival depends on entry, growth, Rickettsia species are transmitted by numerous types of arthropod, including chigger, ticks, fleas, and lice, and are associated with both human and plant disease. Despite the similar name, Rickettsia bacteria do not cause rickets, the majority of Rickettsia bacteria are susceptible to antibiotics of the tetracycline group. The classification of Rickettsia into three groups was based on serology. This grouping has since confirmed by DNA sequencing. All three of these contain human pathogens, the scrub typhus group has been reclassified as a related new genus – Orientia – but many medical textbooks still list this group under the rickettsial diseases. Rickettsia are more widespread than previously believed and are known to be associated with arthropods, leeches, divisions have also been identified in the spotted fever group and this group likely should be divided into two clades. Tsutsugamushi has been reclassified into the genus Orientia, peach phony RLO Papaya Bunchy Top Disease Infection occurs in nonhuman mammals, for example, species of Rickettsia have been found to afflict the South American guanaco, Lama guanacoe. Certain segments of rickettsial genomes resemble those of mitochondria, the deciphered genome of R. prowazekii is 1,111,523 bp long and contains 834 genes. Unlike free-living bacteria, it contains no genes for anaerobic glycolysis or genes involved in the biosynthesis and regulation of amino acids, in this regard, it is similar to mitochondrial genomes, in both cases, nuclear resources are used. ATP production in Rickettsia is the same as that in mitochondria, in fact, of all the microbes known, the Rickettsia is probably the closest relative to the mitochondria. Unlike the latter, the genome of R. prowazekii, however, contains a set of genes encoding for the tricarboxylic acid cycle. Still, the genomes of the Rickettsia, as well as the mitochondria, are said to be small. The recent discovery of another parallel between Rickettsia and viruses may become a basis for fighting HIV infection. A probable reason for this actively studied phenomenon is a degree of homology between the rickettsiae and the virus – namely, common epitope due to common genome fragment in both pathogens. Surprisingly, the other reported to be likely to provide the same effect is the virus-caused illness dengue fever. Comparative analysis of sequences have also identified five conserved signature indels in important proteins which are uniquely found in members of the genus Rickettsia

15.
Amblyomma hebraeum
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Amblyomma hebraeum, commonly known as the South African bont tick, is a species of hard tick that is native to southern Africa. The scutum and alloscutum of the male is dappled in various shades, the females scutum is dappled but the alloscutum is solid black. The alloscutum in both sexes is fringed by prominent festoons, the legs are swarthy or reddish, and paler at the joints. The species is native to eastern and northern South Africa, Swaziland, eastern Botswana, to the north and in Madagascar, the species is replaced by the tropical bont tick, with which it locally overlaps. The nymph and adult stages are vectors for Heartwater disease which affects various species of domesticated ruminants, some wild ruminants are susceptible to the disease and suffer from clinical heartwater, but others are highly resistant. The ticks remain infective for life, but their infection rates vary according to the season and region where they occur, in South Africa 1 to 7 percent of ticks are infected at any one time

16.
Senegal
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Senegal, officially the Republic of Senegal, is a country in West Africa. Senegal is bordered by Mauritania in the north, Mali to the east, Guinea to the southeast, and Guinea-Bissau to the southwest. Senegal also borders The Gambia, a country occupying a narrow sliver of land along the banks of the Gambia River, Senegal also shares a maritime border with Cape Verde. Senegals economic and political capital is Dakar and it is the westernmost country in the mainland of the Old World, or Afro-Eurasia, and owes its name to the Senegal River, which borders it to the east and north. The name Senegal comes from the Wolof Sunuu Gaal, which means Our Boat, Senegal covers a land area of almost 197,000 square kilometres and has an estimated population of about 15 million. The climate is Sahelian, but there is a rainy season, the territory of modern Senegal has been inhabited by various ethnic groups since prehistory. Organized kingdoms emerged around the century, and parts of the country were ruled by prominent regional empires such as the Jolof Empire. The present state of Senegal has its roots in European colonialism, which began during the mid-15th century, the establishment of coastal trading posts gradually led to control of the mainland, culminating in French rule of the area by the 19th century, albeit amid much local resistance. Senegal peacefully attained independence from France in 1960, and has since been among the politically stable countries in Africa. Senegals economy is centered mostly on commodities and natural resources, major industries are fish processing, phosphate mining, fertilizer production, petroleum refining, construction materials, and ship construction and repair. As in most African nations, agriculture is a sector, with Senegal producing several important cash crops, including peanuts, sugarcane, cotton, green beans, tomatoes, melons. Owing to its stability, tourism and hospitality are also burgeoning sectors. A multiethnic and secular nation, Senegal is predominantly Sunni Muslim with Sufi, French is the official language, although many native languages are spoken and recognized. Since April 2012 Senegals president has been Macky Sall, Senegal has been a member of the Organisation internationale de la Francophonie since 1970. Senegal is named after the Senegal River, the etymology of which is contested, one popular theory is that it stems from the Wolof phrase sunu gaal, which means our canoe, resulting from a miscommunication between 15th-century Portuguese sailors and Wolof fishermen. The our canoe theory has been embraced in modern Senegal for its charm. It is frequently used in appeals to national solidarity, frequently heard in the media, modern historians believe the name probably refers to the Sanhaja, Berbers who lived on the northern side of the river. A competing theory is that it derives from the town of Sanghana

17.
Guadeloupe
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Guadeloupe is an insular region of France located in the Leeward Islands, part of the Lesser Antilles in the Caribbean. Administratively, it is a region consisting of a single overseas department. With a land area of 1,628 square kilometres and a population of 400,132 as of January 2015. Guadeloupes two main islands are Basse-Terre to the west and Grande-Terre to the east, which are separated by a strait that is crossed with bridges. They are often referred to as a single island, the department also includes the Dependencies of Guadeloupe, which include the smaller islands of Marie-Galante and La Désirade, and the Îles des Saintes. Guadeloupe, like the other departments, is an integral part of France. As a constituent territory of the European Union and the Eurozone, as an overseas department, however, it is not part of the Schengen Area. The prefecture of Guadeloupe is the city of Basse-Terre, which lies on the island of the same name, the official language is French, and virtually the entire population except recent arrivals from metropolitan France also speak Antillean Creole. Christopher Columbus named the island Santa María de Guadalupe in 1493 after the Virgin Mary, venerated in the Spanish town of Guadalupe, the island was called Karukera by the Arawak people, who settled on there in 300 AD/CE. During the 8th century, the Caribs came and killed the population of Amerindians on the island. During his second trip to the Americas, in November 1493, Christopher Columbus became the first European to land on Guadeloupe, while seeking fresh water. He called it Santa María de Guadalupe de Extremadura, after the image of the Virgin Mary venerated at the Spanish monastery of Villuercas, in Guadalupe, the expedition set ashore just south of Capesterre, but left no settlers behind. Columbus is credited with discovering the pineapple on the island of Guadeloupe in 1493 and he called it piña de Indias, which can be correctly translated as pine cone of the Indies. During the 17th century, the Caribs fought against the Spanish settlers, after successful settlement on the island of St. Due to Martiniques inhospitable nature, the duo resolved to settle in Guadeloupe in 1635, took possession of the island and it was annexed to the kingdom of France in 1674. Over the next century, the British seized the island several times, the economy benefited from the lucrative sugar trade, which commenced during the closing decades of the 17th century. Guadeloupe produced more sugar than all the British islands combined, worth about £6 million a year, the British captured Guadeloupe in 1759. The British government decided that Canada was strategically important and kept Canada while returning Guadeloupe to France in the Treaty of Paris that ended the Seven Years War

18.
Endothelium
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It is a thin layer of simple squamous cells called endothelial cells. Endothelial cells in contact with blood are called vascular endothelial cells. Vascular endothelial cells line the entire system, from the heart to the smallest capillaries. These cells have unique functions in vascular biology and these functions include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the surfaces of the heart chambers is called endocardium. Both blood and lymphatic capillaries are composed of a layer of endothelial cells called a monolayer. In straight sections of a vessel, vascular endothelial cells typically align. Many considered the endothelium a specialized epithelial tissue, excessive or prolonged increases in permeability of the endothelial monolayer, as in cases of chronic inflammation, may lead to tissue edema/swelling. The most prevailing mechanism of endothelial dysfunction is an increase in reactive oxygen species, the signalling protein ERK5 is essential for maintaining normal endothelial cell function

19.
Inflammation
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The classical signs of inflammation are heat, pain, redness, swelling, and loss of function. Inflammation is a response, and therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity. Too little inflammation could lead to tissue destruction by the harmful stimulus. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis, Inflammation is therefore normally closely regulated by the body. Inflammation can be classified as acute or chronic. Acute inflammation is the response of the body to harmful stimuli and is achieved by the increased movement of plasma. A series of biochemical events propagates and matures the inflammatory response, involving the vascular system, the immune system. Inflammation is not a synonym for infection, Inflammation on the other hand describes purely the bodys immunovascular response, whatever the cause may be. But because of how often the two are correlated, words ending in the suffix -itis are sometimes described as referring to infection. There are also situations where microbial invasion does not result in classic inflammatory response—for example, parasitosis. Acute inflammation is a process, usually appearing within a few minutes or hours. It involves a coordinated and systemic mobilisation response locally of various immune, endocrine, in a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and then ceases. It is characterized by five signs, An acronym that may be used to remember the key symptoms is PRISH, for pain, redness, immobility, swelling. Loss of function has multiple causes, Acute inflammation of the lung does not cause pain unless the inflammation involves the parietal pleura, which does have pain-sensitive nerve endings. PAMPs are compounds that are associated with pathogens, but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related injury and cell damage, at the onset of an infection, burn, or other injuries, these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes the redness and increased heat, increased permeability of the blood vessels results in an exudation of plasma proteins and fluid into the tissue, which manifests itself as swelling. Some of the released mediators such as increase the sensitivity to pain

20.
Histology
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Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is commonly performed by examining cells and tissues under a microscope or electron microscope, the specimen having been sectioned, stained. Histological studies may be conducted using tissue culture, where human or animal cells are isolated and maintained in an artificial environment for various research projects. The ability to visualize or differentially identify microscopic structures is frequently enhanced through the use of histological stains, histology is an essential tool of biology and medicine. Trained physicians, frequently licensed pathologists, are the personnel who perform histopathological examination and their field of study is called histotechnology. In the 17th century, Italian Marcello Malpighi invented one of the first microscopes for studying tiny biological entities, Malpighi analysed several parts of the organs of bats, frogs and other animals under the microscope. Malpighi, while studying the structure of the lung, noticed its membranous alveoli and his discovery established how the oxygen we breathe enters the blood stream and serves the body. In the 19th century, histology was a discipline in its own right. The French anatomist Bichat introduced the concept of tissue in anatomy in 1801, the 1906 Nobel Prize in Physiology or Medicine was awarded to histologists Camillo Golgi and Santiago Ramon y Cajal. They had dueling interpretations of the structure of the brain based in differing interpretations of the same images. Cajal won the prize for his theory and Golgi for the staining technique he invented to make it possible. There are four types of animal tissues, muscle tissue, nervous tissue, connective tissue. All tissue types are subtypes of these four basic tissue types and their structure is very different from animal tissues. The most common fixative for light microscopy is 10% neutral buffered formalin, for electron microscopy, the most commonly used fixative is glutaraldehyde, usually as a 2. 5% solution in phosphate buffered saline. These fixatives preserve tissues or cells mainly by irreversibly cross-linking proteins and this can be detrimental to certain histological techniques. Further fixatives are often used for electron microscopy such as osmium tetroxide or uranyl acetate Formalin fixation leads to degradation of mRNA, miRNA and DNA in tissues, however, extraction, amplification and analysis of these nucleic acids from formalin-fixed, paraffin-embedded tissues is possible using appropriate protocols. Frozen section procedure is a way to fix and mount histology sections using a refrigeration device called a cryostat. It is often used after surgical removal of tumors to allow determination of margin

21.
Necrosis
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Necrosis is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by external to the cell or tissue, such as infection, toxins. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death, while apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal. This initiates in the tissue a inflammatory response which attracts leukocytes. However, microbial damaging substances released by leukocytes would create collateral damage to surrounding tissues, too much collateral damage would inhibit the healing process. Thus, untreated necrosis results in a build-up of decomposing dead tissue, for this reason, it is often necessary to remove necrotic tissue surgically, a procedure known as debridement. Coagulation occurs as a result of protein denaturation, causing albumin to transform into a firm and this pattern of necrosis is typically seen in hypoxic environments, such as infarction. Coagulative necrosis occurs primarily in tissues such as the kidney, heart, severe ischemia most commonly causes necrosis of this form. Liquefactive necrosis, in contrast to necrosis, is characterized by the digestion of dead cells to form a viscous liquid mass. This is typical of bacterial, or sometimes fungal, infections because of their ability to stimulate an inflammatory response, the necrotic liquid mass is frequently creamy yellow due to the presence of dead leukocytes and is commonly known as pus. Gangrenous necrosis can be considered a type of coagulative necrosis that resembles mummified tissue and it is characteristic of ischemia of lower limb and the gastrointestinal tracts. The necrotic tissue appears as white and friable, like clumped cheese, dead cells disintegrate but are not completely digested, leaving granular particles. Microscopic examination shows amorphous granular debris enclosed within a distinctive inflammatory border, fat necrosis is specialized necrosis of fat tissue, resulting from the action of activated lipases on fatty tissues such as the pancreas. Calcium, magnesium or sodium may bind to these lesions to produce a chalky-white substance, the calcium deposits are microscopically distinctive and may be large enough to be visible on radiographic examinations. To the naked eye, calcium deposits appear as gritty white flecks, fibrinoid necrosis is a special form of necrosis usually caused by immune-mediated vascular damage. It is marked by complexes of antigen and antibodies, sometimes referred to as “immune complexes” deposited within arterial walls together with fibrin, there are also very specific forms of necrosis such as gangrene, gummatous necrosis and hemorrhagic necrosis. Some spider bites may lead to necrosis, in the United States, only spider bites from the brown recluse spider reliably progress to necrosis. In other countries, spiders of the genus, such as the Chilean recluse in South America, are also known to cause necrosis

22.
Immunity (medical)
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Immunity is the capability of multicellular organisms to resist harmful microorganisms from entering it. Immunity involves both specific and nonspecific components, the nonspecific components act as barriers or eliminators of a wide range of pathogens irrespective of their antigenic make-up. Other components of the immune system adapt themselves to each new disease encountered and are able to generate pathogen-specific immunity, an immune system may contain innate and adaptive components. The innate system in mammalians for example is composed of bone marrow cells that are programmed to recognise foreign substances. The adaptive system is composed of more advanced lymphatic cells that are programmed to recognise self substances, the reaction to foreign substances is etymologically described as inflammation, meaning to set on fire. The non-reaction to self substances is described as immunity, meaning to exempt or as immunotolerance, disease can arise when what is foreign cannot be eliminated or what is self is not spared. Innate immunity, also called native immunity, exists by virtue of an organisms constitution and it is divided into two types, Non-Specific innate immunity, a degree of resistance to all infections in general. Specific innate immunity, a resistance to a kind of microorganism only. As a result some races, specific individuals or breeds in agriculture do not suffer from certain infectious diseases, passive immunity is acquired through transfer of antibodies or activated T-cells from an immune host, it is short lived—usually lasting only a few months. The diagram below summarizes these divisions of immunity, humoral immunity is called active when the organism generates its own antibodies, and passive when antibodies are transferred between individuals or species. Similarly, cell mediated immunity is active when the organisms’ own T-cells are stimulated, the concept of immunity has intrigued mankind for thousands of years. Between the time of Hippocrates and the 19th century, when the foundations of the methods were laid. If someone were exposed to the miasma in a swamp, in evening air, or breathing air in a sickroom or hospital ward, the modern word immunity derives from the Latin immunis, meaning exemption from military service, tax payments or other public services. For no one was attacked a second time, or not with a fatal result. The term immunes, is found in the epic poem Pharsalia written around 60 B. C. by the poet Marcus Annaeus Lucanus to describe a North African tribes resistance to snake venom. In the treatise, Al Razi describes the presentation of smallpox. The first scientist who developed full theory of immunity was Ilya Mechnikov after he revealed phagocytosis in 1882, the birth of active immunotherapy may have begun with Mithridates VI of Pontus. To induce active immunity for snake venom, he recommended using a similar to modern toxoid serum therapy

23.
Tropical disease
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Tropical diseases are diseases that are prevalent in or unique to tropical and subtropical regions. The diseases are prevalent in temperate climates, due in part to the occurrence of a cold season. However, many were present in northern Europe and northern America in the 17th and 18th centuries before modern understanding of disease causation, the initial impetus for tropical medicine was to protect the health of colonialists, notably in India under the British Raj. Insects such as mosquitoes and flies are by far the most common disease carrier and these insects may carry a parasite, bacterium or virus that is infectious to humans and animals. Most often disease is transmitted by a bite, which causes transmission of the infectious agent through subcutaneous blood exchange. Vaccines are not available for most of the diseases listed here, tDRs vision is to foster an effective global research effort on infectious diseases of poverty in which disease endemic countries play a pivotal role. It has a mission of developing new tools and strategies against these diseases. The TDR secretariat is based in Geneva, Switzerland, but the work is conducted throughout the world through many partners, TDR history The current TDR disease portfolio includes the following entries, Chagas disease is a parasitic disease which occurs in the Americas, particularly in South America. Between 16 and 18 million people are currently infected, dengue Helminths African trypanosomiasis or sleeping sickness, is a parasitic disease, caused by protozoa called trypansomes. Leprosy† is a infectious disease caused by Mycobacterium leprae. Leprosy is primarily a disease of the peripheral nerves and mucosa of the upper respiratory tract. Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs, lymphatic filariasis is a parasitic disease caused by thread-like parasitic filarial worms called nematode worms, all transmitted by mosquitoes. Loa loa is another filarial parasite transmitted by the deer fly,120 million people are infected worldwide. It is carried by over half the population in the most severe endemic areas, the most noticeable symptom is elephantiasis, a thickening of the skin and underlying tissues. Elephantiasis is caused by infection by filarial worms in the lymph nodes. This clogs the lymph nodes and slows the draining of lymph fluid from a portion of the body, malaria Caused by a Protozoan parasites transmitted by female Anopheles mosquitoes, as they are the blood-feeders. The disease is caused by species of the genus Plasmodium, malaria infected an estimated 190-311 million people in 2008 and 708, 000-1,003,000 died mostly in Sub-Sahara Africa. Onchocerciasis or river blindness is the second leading infectious cause of blindness

24.
C-reactive protein
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C-reactive protein is an annular, pentameric protein found in blood plasma, whose levels rise in response to inflammation. It is a protein of hepatic origin that increases following interleukin-6 secretion by macrophages. Its physiological role is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells in order to activate the complement system via the C1Q complex, CRP is synthesized by the liver in response to factors released by macrophages and fat cells. It is a member of the family of proteins. It is not related to C-peptide or protein C, C-reactive protein was the first pattern recognition receptor to be identified. CRP was so named because it was first identified as a substance in the serum of patients with acute inflammation that reacted with the somatic C carbohydrate antigen of Pneumococcus. Discovered by Tillett and Francis in 1930, it was thought that CRP might be a pathogenic secretion since it was elevated in a variety of illnesses. The later discovery of hepatic synthesis demonstrated that it is a native protein, the CRP gene is located on the first chromosome. It is a member of the pentraxins family. It has 224 amino acids, has a molecular mass of 25,106 Da. CRP binds to the phosphocholine expressed on the surface of dead or dying cells and this activates the complement system, promoting phagocytosis by macrophages, which clears necrotic and apoptotic cells and bacteria. These conditions cause release of interleukin-6 and other cytokines that trigger the synthesis of CRP, CRP binds to phosphocholine on micro-organisms. It is thought to assist in complement binding to foreign and damaged cells and enhances phagocytosis by macrophages and it plays a role in innate immunity as an early defense system against infections. CRP rises within two hours of the onset of inflammation, up to a 50, 000-fold, and peaks at 48 hours and its half-life of 18 hours is constant, and therefore its level is determined by the rate of production and hence the severity of the precipitating cause. CRP is thus a marker for inflammation that can be used to screen for inflammation, CRP is used mainly as a marker of inflammation. Apart from liver failure, there are few known factors that interfere with CRP production, ELISA, immunoturbidimetry, nephelometry, rapid immunodiffusion, and visual agglutination are all methods used to measure CRP. A high-sensitivity CRP test measures low levels of CRP using laser nephelometry, the test gives results in 25 minutes with a sensitivity down to 0.04 mg/L. Higher levels are found in pregnant women, mild inflammation and viral infections, active inflammation, bacterial infection

25.
Growth medium
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A growth medium or culture medium is a solid or liquid or semi-solid designed to support the growth of microorganisms or cells, or small plants like the moss Physcomitrella patens. Different types of media are used for growing different types of cells, the most common growth media for microorganisms are nutrient broths and agar plates, specialized media are sometimes required for microorganism and cell culture growth. Some organisms, termed fastidious organisms, require specialized environments due to nutritional requirements. Viruses, for example, are intracellular parasites and require a growth medium containing living cells. The most common media for microorganisms are nutrient broths or LB medium. Liquid media are often mixed with agar and poured via a media dispenser into Petri dishes to solidify. These agar plates provide a medium on which microbes may be cultured. They remain solid, as very few bacteria are able to decompose agar, bacteria grown in liquid cultures often form colloidal suspensions. In the case of cells, this difficulty is often addressed by the addition of blood serum or a synthetic serum replacement to the medium. In the case of microorganisms, no such limitations exist, as they are often unicellular organisms. One other major difference is that cells in culture are often grown on a flat surface to which they attach, and the medium is provided in a liquid form. In contrast, bacteria such as Escherichia coli may be grown on solid or in liquid media, an important distinction between growth media types is that of defined versus undefined media. A defined medium will have known quantities of all ingredients, for microorganisms, they consist of providing trace elements and vitamins required by the microbe and especially defined carbon and nitrogen sources. Glucose or glycerol are used as carbon sources, and ammonium salts or nitrates as inorganic nitrogen sources. An undefined medium has some complex ingredients, such as yeast extract or casein hydrolysate, undefined media are sometimes chosen based on price and sometimes by necessity – some microorganisms have never been cultured on defined media. A good example of a medium is the wort used to make beer. The wort contains all the nutrients required for yeast growth, and under anaerobic conditions, when the fermentation process is complete, the combination of medium and dormant microbes, now beer, is ready for consumption. Minimal media can also be used to select for or against recombinants or exconjugants and this supplementation allows for the culturing of specific lines of auxotrophic recombinants

26.
Biological hazard
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Biological hazards, also known as biohazards, refer to biological substances that pose a threat to the health of living organisms, primarily that of humans. This can include medical waste or samples of a microorganism, virus or toxin that can affect human health and it can also include substances harmful to other animals. The term and its symbol are generally used as a warning. The biohazard symbol was developed in 1966 by Charles Baldwin, an engineer working for the Dow Chemical Company on the containment products. It is used in the labeling of biological materials that carry a significant health risk, including viral samples, in Unicode, the biohazard symbol is U+2623. Category B, UN3373 – Biological substance transported for diagnostic or investigative purposes, regulated Medical Waste, UN3291 – Waste or reusable material derived from medical treatment of an animal or human, or from biomedical research, which includes the production and testing. The United States Centers for Disease Control and Prevention categorizes various diseases in levels of biohazard, Level 1 being minimum risk, Laboratories and other facilities are categorized as BSL 1-4 or as P1 through P4 for short. Biohazard Level 1, Bacteria and viruses including Bacillus subtilis, canine hepatitis, Escherichia coli, varicella, as well as cell cultures. At this level precautions against the materials in question are minimal, most likely involving gloves. Routine diagnostic work with clinical specimens can be done safely at Biosafety Level 2, research work can be done in a BSL-2 facility, using BSL-3 practices and procedures. Variola virus is an agent that is worked with at BSL-4 despite the existence of a vaccine, when dealing with biological hazards at this level the use of a positive pressure personnel suit, with a segregated air supply, is mandatory. Multiple airlocks are employed and are secured to prevent both doors opening at the same time. All air and water going to and coming from a Biosafety Level 4 lab will undergo similar decontamination procedures to eliminate the possibility of an accidental release. Currently there are no bacteria classified at this level, the biohazard symbol was developed by the Dow Chemical Company in 1966 for their containment products. In an article he wrote for Science in 1967, the symbol was presented as the new standard for all biological hazards, the chosen symbol scored the best on nationwide testing for memorability. The design was first specified in 39 FR23680 but was dropped in the succeeding amendment, however, various US states adopted the specification for their state code. Biological agent Biosafety level Biocontainment Planetary protection and Interplanetary contamination Public health Biosafety in Microbiological and Biomedical Laboratories, Prevention of Biological Hazards, EU-OSHA Symbol Making, an account of the development of the symbol in 1966. BioSeal Systems, Biosafety level 4 containment, Biohazard Remediation Compliance Overview Example of Reclassified Biohazard to Level 4, article from The Lancet concerning the reclassification of Ebola after observation

27.
Josamycin
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It is synthesized from strains of Streptomyces narbonensis var. josamyceticus var. nova Currently sold in various countries. Brand examples are, Europe, Josalid, Josacine, Iosalide, there has been a case report of oedema of the feet

28.
PubMed Identifier
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PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval, from 1971 to 1997, MEDLINE online access to the MEDLARS Online computerized database primarily had been through institutional facilities, such as university libraries. PubMed, first released in January 1996, ushered in the era of private, free, home-, the PubMed system was offered free to the public in June 1997, when MEDLINE searches via the Web were demonstrated, in a ceremony, by Vice President Al Gore. Information about the journals indexed in MEDLINE, and available through PubMed, is found in the NLM Catalog. As of 5 January 2017, PubMed has more than 26.8 million records going back to 1966, selectively to the year 1865, and very selectively to 1809, about 500,000 new records are added each year. As of the date,13.1 million of PubMeds records are listed with their abstracts. In 2016, NLM changed the system so that publishers will be able to directly correct typos. Simple searches on PubMed can be carried out by entering key aspects of a subject into PubMeds search window, when a journal article is indexed, numerous article parameters are extracted and stored as structured information. Such parameters are, Article Type, Secondary identifiers, Language, publication type parameter enables many special features. As these clinical girish can generate small sets of robust studies with considerable precision, since July 2005, the MEDLINE article indexing process extracts important identifiers from the article abstract and puts those in a field called Secondary Identifier. The secondary identifier field is to store numbers to various databases of molecular sequence data, gene expression or chemical compounds. For clinical trials, PubMed extracts trial IDs for the two largest trial registries, ClinicalTrials. gov and the International Standard Randomized Controlled Trial Number Register, a reference which is judged particularly relevant can be marked and related articles can be identified. If relevant, several studies can be selected and related articles to all of them can be generated using the Find related data option, the related articles are then listed in order of relatedness. To create these lists of related articles, PubMed compares words from the title and abstract of each citation, as well as the MeSH headings assigned, using a powerful word-weighted algorithm. The related articles function has been judged to be so precise that some researchers suggest it can be used instead of a full search, a strong feature of PubMed is its ability to automatically link to MeSH terms and subheadings. Examples would be, bad breath links to halitosis, heart attack to myocardial infarction, where appropriate, these MeSH terms are automatically expanded, that is, include more specific terms. Terms like nursing are automatically linked to Nursing or Nursing and this important feature makes PubMed searches automatically more sensitive and avoids false-negative hits by compensating for the diversity of medical terminology. The My NCBI area can be accessed from any computer with web-access, an earlier version of My NCBI was called PubMed Cubby

Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on …

Photomicrograph of a histological section of human skin prepared for direct immunofluorescence using an anti-IgA antibody. The skin is from a patient with Henoch–Schönlein purpura: IgA deposits are found in the walls of small superficial capillaries (yellow arrows). The pale wavy green area on top is the epidermis, the bottom fibrous area is the dermis.

These figures demonstrates the basic mechanism of immunofluorescence. Primary immunofluorescence is depicted to the left, which shows an antibody with a fluorophore group bound to it directly binding to the epitope of the antigen it’s specific for. Once the antibody binds to the epitope, the sample can be viewed under fluorescent microscope to confirm the presence of the antigen in the sample. Conversely, secondary immunofluorescence is depicted to the right, which shows that first an untagged primary antibody binds to the epitope of the antigen in a mechanism similar to the one described above. However, after the primary antibodies have bound to their target, a secondary antibody (tagged with a fluorophore) comes along. This secondary antibody’s binding sites are specific for the primary antibody that’s already bound to the antigen, and therefore the secondary antibody binds to the primary antibody. This method allows for more fluorophore-tagged antibodies to attach to their target, thus increasing the fluorescent signal during microscopy.

Photomicrograph of a histological section of human skin prepared for direct immunofluorescence using an anti-IgG antibody. The skin is from a patient with systemic lupus erythematosus and shows IgG deposit at two different places: The first is a band-like deposit along the epidermal basement membrane ("lupus band test" is positive). The second is within the nuclei of the epidermal cells (anti-nuclear antibodies).